For treating diabetes, blood sugar regulators such as insulin and synthetic hypoglycemic agents have been conventionally used widely. Diabetes is a disease which accompanies various complications which are hardly prevented from developing by a mere control of the blood sugar, and a new therapeutic agent for the complications of diabetes has been demanded. Accumulation of and increase in sorbitol and galactitol in tissues which are caused by chronic hyperglycemia have recently been drawing attention as the mechanism of the onset of the complications of diabetes.
Some literatures suggest that a compound having an inhibitory action on the activity of aldose reductase, which is an enzyme capable of converting aldose such as glucose or galactose into sorbitol or galactitol, is useful for the treatment of the complications of diabetes, such as faulty union of corneal injury, cataract, neurosis, nephropathy and retinopathy [see J. H. Kinoshita et al., Biochem. Biophys, Acta, 158, 472 (1968), Richard Poulson et al. Biochem. Pharmacol., 2, 1495 (1983) and D. Dvornik et al., Science, 182, 1145 (1973)].
Based on the foregoing, the study is directed to the prevention and treatment of the complications of diabetes by the inhibition of aldose reductase activity to ultimately inhibit accumulation of polyols such as sorbitol and galactitol.
Of the compounds synthesized for this end, various 1,4-benzothiazine-4-acetic acid derivatives have aldose reductase inhibitory action as reported in Japanese Patent Unexamined Publication Nos. 40264/1986 and 107970/1988. Yet, the development of a therapeutic agent for the complications of diabetes, which has a still more excellent aldose reductase inhibitory action, is desired.